Direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP secretion and extent of coronary artery stenosis in patients with stable coronary artery disease.

BACKGROUND: It is unclear whether coronary artery stenosis affects the secretion of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) from the heart independent of ventricular dysfunction. Therefore, this study evaluated the relationship between BNP and NT-proBNP secretion, plasma levels and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels of BNP and NT-proBNP in the aortic root (AO) and coronary sinus (CS) in 251 consecutive patients with stable CAD were measured. The transcardiac increase of NT-proBNP was significantly increased with the severity of coronary artery stenosis (p=0.012), but that of BNP was not (p=0.116). The molar ratio of the (CS-AO) NT-pro-BNP/(CS-AO) BNP increased with the severity of coronary artery stenosis (p=0.019) and decreased after coronary revascularization (p=0.018, n=36). Step-wise multivariate linear regression analyses were used to detect independent predictors of the (CS-AO) NT-proBNP among 10 variables including hemodynamic parameters and the Gensini score, which is a measure of the extent and severity of CAD. Among these variables, left ventricular ejection fraction (p<0.0001), left ventricular end-diastolic pressure (p=0.003) and log Gensini score (p=0.008) were significant independent predictors. CONCLUSION: These findings suggest that the transcardiac increase of NT-proBNP from the heart increases with the severity of coronary artery stenosis independent of hemodynamic overload, and plasma NT-proBNP may be superior to BNP to assess disease severity in CAD patients.     

Relationship between brain natriuretic peptide and coronary stenosis: influence of aging

OBJECTIVES: The relationship between brain natriuretic peptide (BNP) and coronary stenosis, and the utility of BNP for the prediction of coronary stenosis were investigated. METHODS: This study included 100 consecutive patients (48 men, 52 women, mean age 65.8 +/- 9.9 years) who underwent elective cardiac catheterization for the diagnosis of coronary stenosis without other heart diseases (heart failure, valvular heart disease, cardiomyopathy, sick sinus syndrome), and E/A was recorded by echocardiography. The relationship between coronary stenosis, left ventricular ejection fraction by left ventriculography, left ventricular end-diastolic pressure, E/A, left ventricular stroke volume index by echocardiography and BNP were investigated. RESULTS: Thirty-nine patients revealed coronary stenosis > or = 75% (CS), and 6 patients had chronic total occlusion. In the CS(+) group, BNP and left ventricular end-diastolic pressure were elevated significantly (50.7 +/- 48.5 vs 22.1 +/- 21.6 pg/ml, p < 0.05; 9.2 +/- 5.3 vs 6.4 +/- 3.4 mmHg, p < 0.05). In logistic regression analysis, BNP and left ventricular end-diastolic pressure had significant correlations with CS(+), independent of age, systolic blood pressure, E/A and left ventricular ejection fraction (p = 0.007, p = 0.05, respectively). Prognostic values of BNP (> 20 pg/ml) for the diagnosis of CS(+) were sensitivity of 79%, and specificity of 61% (p < 0.005). In the CS(-) group, the patients showing BNP > 20 pg/ml were older than the patients showing BNP < or = 20 pg/ml (68.4 +/- 8.5 vs 60.0 +/- 9.4, p < 0.05). Therefore, the prognostic values were reduced (sensitivity 78%, specificity 82%, p < 0.005) in the younger group (age < 65, n = 42). Even in patients with coronary stenosis but without chronic total occlusion, both BNP and left ventricular end-diastolic pressure were elevated significantly compared with the patients without coronary stenosis (22.1 +/- 21.6 vs 44.0 +/- 43.2 pg/ml, p < 0.01; 6.4 +/- 3.4 vs 9.1 +/- 5.2 mmHg, p < 0.01). CONCLUSIONS: Plasma BNP levels are useful markers for detecting coronary stenosis, especially in younger patients.     

Demographic, clinical and echocardiographic determinants of B-type natriuretic peptide plasma concentration. A population-based study.

INTRODUCTION: The aim of this study was to identify determinants of plasma B-type natriuretic peptide (BNP) levels at the population level. METHODS: In a cross-sectional study, the authors evaluated 559 community subjects aged > or = 45 years. The association between plasma BNP concentration and the hypothesized determinants was assessed by linear regression using the natural logarithm of BNP plasma concentration as the dependent variable and separate models for each gender. RESULTS: Plasma BNP was significantly higher in women. BNP increased with age, more steeply in men than women (p < 0.05 for the interaction). In univariate analysis, BNP was associated with left ventricular systolic dysfunction (LVSD), moderate to severe valvular abnormalities, left atrial diameter/body surface area, left ventricular mass index, systolic blood pressure, lower creatinine clearance and jugular venous distension. In women it was also associated with left ventricular end-diastolic diameter/body surface area and atrial fibrillation, and in men with changes in the segmental wall motion index. The final multivariate models included age, LVSD and left atrial size as significant independent determinants of BNP level, explaining 16.8% and 32.3% of BNP variability in women and men respectively. CONCLUSION: The association between BNP and left atrial size independently of systolic dysfunction suggests that BNP might reflect subclinical diastolic abnormaltes. False positive BNP levels for the diagnosis of left ventricular systolic dysfunction and heart failure are probably due to high BNP levels in people with cardiac abnormalities not detected by echocardiography.     

Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function

OBJECTIVES: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone. METHODS: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function. RESULTS: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001). CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.     

Clinical significance of acute-phase endothelin-1 in acute myocardial infarction patients treated with direct coronary angioplasty.

BACKGROUND: The aim of the present study was to investigate the relationship between plasma concentrations of endothelin (ET)-1 and clinical outcome (including mortality) and left ventricular (LV) systolic function in acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 110 consecutive first-AMI patients who were successfully reperfused by primary coronary intervention. Plasma ET-1 concentrations were evaluated 24 h from onset and the patients were divided into 2 groups according to the median value, either a high group (H group: > or = 2.90 pg/ml plasma ET-1; n = 55) or low group (L group: < 2.90 pg/ml plasma ET-1; n = 55). Major complications and LV systolic function were monitored in the 2 groups. Both highly sensitive C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP) showed a significant positive correlation with ET-1 (BNP: r = 048, p < 0.0001, hs-CRP: r = 0.43, p < 0.001). Chronic stage left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI) were significantly poorer in the H group (LVEF: 51+/-15% vs 60+/-13%, p = 0.003, LVEDVI: 74+/-19 ml/m2 vs 66+/-14 ml/m2, p < 0.05). There were significantly more major complications in the H group than in the L group (cardiogenic shock: 18% vs 5%, p = 0.04; cardiac death: 13% vs 0%, p < 0.01). CONCLUSIONS: In the setting of AMI, plasma ET-1 concentrations may be closely related to LV systolic dysfunction and poor patient outcome, including mortality.     

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction

OBJECTIVE—To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction.
SETTING—Tertiary cardiovascular referral centre.
METHODS—Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in 21 asymptomatic or minimally symptomatic patients with chronic right ventricular pressure overload caused by congenital heart disease, and in seven healthy volunteers. Right ventricular ejection fraction was determined using magnetic resonance imaging.
RESULTS—Right ventricular ejection fraction in the volunteers was higher than in the patients (69.0 (8.2)% v 58.0(12.0)%, respectively; p < 0.006). Left ventricular ejection fraction was 72.3(7.8)% in volunteers and 68.1(11.0)% in patients (NS). There was a significant difference between patients and volunteers in the plasma concentrations of BNP (5.3 (3.5) v 2.3 (1.7) pmol/l, respectively; p < 0.009) and ANP (7.3 (4.5) v 3.6 (1.4) pmol/l; p < 0.05). In both patients and volunteers, mean plasma ANP was higher than mean plasma BNP. Right ventricular ejection fraction was inversely correlated with BNP and ANP (respectively, r = 0.65; p < 0.0002 and r = 0.61; p < 0.002). There was no correlation between left ventricular ejection fraction and BNP (r = 0.2; NS) or ANP (r = 0.52; NS). Similarly, no correlation was shown between the level of right ventricular systolic pressure and either plasma BNP (r = 0.20) or plasma ANP (r = 0.07).
CONCLUSIONS—There was a significant inverse correlation between right ventricular ejection fraction and the plasma neurohormones BNP and ANP in asymptomatic or minimally symptomatic patients with right ventricular pressure overload and congenital heart disease. Monitoring changes in BNP and ANP may provide quantitative follow up of right ventricular dysfunction in these patients.


Keywords: natriuretic peptides; right ventricle; pressure overload; congenital heart disease     

Prognostic value of neurohormonal activation and cardiopulmonary exercise testing in patients with chronic heart failure

We compared the value of plasma neurohormones and cardiopulmonary exercise testing for predicting long-term prognosis in patients with moderate congestive heart failure (CHF). We studied 264 consecutive patients with CHF due to left ventricular systolic dysfunction. Plasma atrial natriuretic peptide (ANP), norepinephrine, and endothelin-1 were measured at rest in all patients, who also underwent a symptom-limited maximal exercise with oxygen consumption (VO(2)) determination. After a median follow-up of 789 days, 52 deaths and 31 heart transplantations occurred, of which 4 were urgent. In an univariate analysis, New York Heart Association functional class, systolic blood pressure at rest, left ventricular end-diastolic diameter, left ventricular ejection fraction, peak VO(2), percent of predicted peak VO(2), plasma ANP, plasma norepinephrine, and plasma endothelin-1 were associated with survival without urgent heart transplantation. In a multivariate stepwise regression analysis, only plasma ANP (p = 0.0001), left ventricular ejection fraction (p = 0.007), and plasma norepinephrine (p = 0.035), but neither peak VO(2) nor percentage of predicted peak VO(2), were independent predictors of death or urgent heart transplantation. Determination of plasma ANP and norepinephrine provides additional independent information for long-term prognostic determination compared with exercise testing alone. Measurement of plasma neurohormones should therefore be considered routinely as a complementary or alternative tool for identifying high-risk patients with moderate CHF.     

B-type natriuretic peptide in patients with clinical hyperthyroidism

AIMS: To investigate the level and clinical significance of plasma B-type natriuretic peptide (BNP) in patients with hyperthyroidism. METHODS: Plasma BNP was measured in 32 healthy subjects and 67 patients with clinical hyperthyroidism. Left ventricular anatomy and function was assessed with echocardiography. RESULTS: The average BNP in hyperthyroid patients was higher than that in healthy subjects (186+/-140 vs 34+/-17 ng/l, p =0.001). The increase in BNP was mainly found in hyperthyroid patients who had clinical and echocardiographic evidence of left ventricular dysfunction (250+/-190 ng/l). The BNP level in patients with hyperthyroidism, but with normal left ventricular function, was similar to that of the controls (37+/-17 vs 34+/-17, ng/l, p>0.05). Multi-regression analysis showed that left atrial diameter and left ventricular ejection fraction were independently associated with the plasma levels of BNP. CONCLUSIONS: there is a significant elevation in plasma BNP in patients with hyperthyroidism; the increase is largely due to hyperthyroidism-induced left ventricular dysfunction. Measurements of plasma BNP may help to detect heart failure in patients with clinical hyperthyroidism.     

Why is the concentration of plasma brain natriuretic peptide in elderly inpatients greater than normal?

BACKGROUND: Higher than normal levels of plasma brain natriuretic peptide (BNP) are often found in elderly patients without overt heart failure. OBJECTIVE: To investigate the relationships between echocardiographic findings and levels of BNP in inpatients undergoing rehabilitation. METHODS: Ejection fraction, early-to-atrial peak transmitral velocity ratio (EAR) and left ventricular mass index were calculated. The patients were 34 men and 83 women, aged 83.4 +/- 0.8 years (mean +/- SEM). RESULTS: The average BNP was 3.5 times higher than the normal range. Age of and BNP level in patients with mild renal dysfunction were significantly greater than age of and BNP level in those with normal renal function. BNP level in patients with left ventricular hypertrophy (LVH) was higher than that in patients without LVH, and there was a positive correlation between left ventricular mass index and BNP level. However, there was no difference between BNP levels of patients with ejection fraction < 50% and > or = 50% (n = 27 versus 90, ejection fractions 40 versus 64%, BNP levels 22.6 +/- 4.0 versus 17.5 +/- 1.6 pmol/l). Moreover, even elderly inpatients without LVH, without cardiovascular diseases, with sinus rhythm, with normal renal function, and with normal left ventricle systolic function had BNP levels that were greater than normal (n = 21, BNP level 11.0 +/- 1.5 pmol/l). We measured EAR of 76 of 90 patients with normal left ventricle systolic function, and 72 of the 76 patients had EAR < 1. CONCLUSION: These results indicate that renal dysfunction and systolic dysfunction as well as cardiac hypertrophy and lower than normal diastolic function contribute to the elevation of BNP levels in elderly inpatients who do not have overt heart failure.     

保留收缩功能性心力衰竭与B型脑钠肽及尿酸的相关性研究

目的结合超声心动图参数探讨B型脑钠肽（brain natriuretic peptide,BNP）联合尿酸（uric acid,UA）对保留收缩功能性心力衰竭诊断的临床意义。方法顺序入选130例有器质性心脏病、纽约心脏协会（New York heart association,NYHA）心功能分级I～IV级的住院患者,其超声心动图提示有不同程度的舒张功能障碍且左心室射血分数（left ventricular ejection fraction,LVEF）≥45%,检测血浆B型脑钠肽、尿酸浓度,按照NYHA分级及BNP浓度进行分组,比较患者的临床指标及超声心动图参数;分别以NYHA分级及BNP为因变量进行多元线性回归分析;对100ng/L400ng/L组较BNP〈100ng/L组的年龄、血浆UA浓度、左心房内径、左心室舒张末期内径、E/E′及左心室质量明显升高,LVEF明显降低,房性心律失常发生率明显升高,差异均有统计学意义（P〈0.01）。经多元线性回归分析仅NYHA分级及E/E′是影响血浆BNP浓度的独立相关因素（r=0.33,P〈0.01;r=0.17,P〈0.05）。100ng/L     

Brain natriuretic peptide (BNP) in coronary insufficiency: relationship with left ventricular filling and exercise tolerance

Brain natriuretic peptide (BNP) is a recently discovered peptide, secreted by the atria and ventricles in response to parietal distension. It was recently proposed as a screening test for left ventricular failure. The authors assayed this peptide at rest in 37 patients with chronic heart failure due to left ventricular systolic dysfunction and another 20 patients with various diseases (respiratory failure, cirrhosis, heart transplantation, "diastolic" heart failure) but normal left ventricular systolic function. A significant increase compared to normal values was observed not only in the group of heart failure patients, but also in patients with all other diseases. BNP was significantly higher in NYHA class IV patients. The relationship between plasma BNP levels and ejection fraction was not significant. On the other hand, a good correlation was observed between BNP and left ventricular filling parameters evaluated by cardiac Doppler: E wave deceleration time (r = -0.53, p = 0.001), E/A ratio: r = 0.57 p = 0.005) or VO2 max (r = -0.55, p < 0.005).     

Elevated levels of brain natriuretic peptide as a predictor of impaired coronary endothelial function in patients with left ventricular remodeling

BACKGROUND: Plasma levels of brain natriuretic peptide (BNP) correlate with left ventricular remodeling, but the relationship between BNP induction and coronary function remains unclear. OBJECTIVES: The present study assessed BNP production in response to left ventricular enlargement and investigated the relationship between BNP production and coronary vasodilating function in patients with left ventricular remodeling. METHODS: Patients (n = 63) with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined using intracoronary acetylcholine, papaverine and nitroglycerin using a Doppler guidewire. RESULTS: Left ventricular end-diastolic dimension was positively correlated with BNP (r = 0.45, p < 0.001) in all patients. BNP was significantly and inversely correlated with percentage change in coronary artery diameter induced by acetylcholine (r = -0.56, p < 0.001) but not by nitroglycerin (r = -0.20, p = 0.28) in patients with left ventricular end-diastolic dimension > or = 55 mm (n = 32). By contrast, BNP was not significantly correlated with percentage change in coronary artery diameter induced by either acetylcholine or nitroglycerin in patients with left ventricular end-diastolic dimension < 55 mm (n = 31). Further, BNP was not correlated with the percentage change in coronary blood flow induced by acetylcholine or by papaverine in patients with or without left ventricular remodeling. CONCLUSIONS: The elevation in plasma BNP levels that occurs in association with left ventricular enlargement is a predictor of impaired endothelium-dependent vasodilation in conductance coronary arteries.     

Marked Elevation of Brain Natriuretic Peptide Levels in Pericardial Fluid Is Closely Associated With Left Ventricular Dysfunction

Objectives. The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid.Background. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides.Methods. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery.Results. The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074).Conclusions. BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.     

Myocardial stiffness is an important determinant of the plasma brain natriuretic peptide concentration in patients with both diastolic and systolic heart failure.

AIMS: Plasma brain natriuretic peptide (BNP) concentration increases in proportion to heart failure (HF) severity. Although plasma BNP decreases to a certain level by optimal treatment, there is significant heterogeneity in the baseline value among individuals. The underlying mechanism of the steady-state plasma BNP levels remains still controversial. We investigated the hypothesis that myocardial stiffness (K(m)) is a major determinant of the plasma BNP level. METHODS AND RESULTS: In 19 patients with diastolic HF [DHF; left ventricular ejection fraction (LVEF) > or =4 5%], 18 with systolic HF (SHF; LVEF < 45%), and 12 controls, left ventricular (LV) performance variables and the results of the stress-strain analyses were obtained by the combined simultaneous measurement of echocardiographic and haemodynamic data, and compared with the plasma BNP level. In DHF, a significant correlation was observed between plasma BNP and fractional shortening (P = 0.010), pulmonary capillary wedge pressure (P = 0.030), end-diastolic pressure (P = 0.006), time constant of the LV isovolumic-pressure decline (P = 0.049), end-diastolic stress (P = 0.012), and K(m) (P = 0.004), respectively. In SHF, a significant correlation was observed between plasma BNP and end-diastolic stress (P = 0.036), chamber stiffness (P = 0.048), and K(m) (P = 0.003), respectively. CONCLUSION: In stable conditions, K(m) may be the most important determinant of the plasma BNP production in patients with both DHF and SHF.     

Doppler echocardiography-derived index of myocardial performance (TEI index): comparison with brain natriuretic peptide levels in various heart disease.

Plasma brain natriuretic peptide (BNP) has diagnostic and prognostic value in heart failure. Cardiac dysfunction varies from systolic or diastolic dysfunction alone to the combination of both. In the present study, Doppler echocardiographic parameters, including the Doppler echocardiography-derived index (TEI index), were compared with plasma BNP levels in 74 patients with various heart diseases. Blood sampling was performed before an echocardiographic examination was conducted. The TEI index was defined as the summation of isovolumic contraction and relaxation time divided by ejection time. In patients with left ventricular (LV) systolic dysfunction (ejection fraction <50%), the TEI index and BNP were increased significantly compared with patients with normal LV systolic function (p<0.05). Patients with a TEI index > or =0.45 showed significantly increased BNP levels compared with patients with a TEI index <0.45, irrespective of LV systolic function (241.4+/-451.2 vs 65.9+/-81.8pg/ml; p<0.05). The TEI index was significantly higher in patients with a BNP > or =73pg/ml than in patients with BNP <73pg/ml (0.57+/-0.24 vs 0.46+/-0.17; p<0.05). Other echocardiographic parameters did not correlate significantly with levels of plasma BNP. Of the echocardiographic parameters, a simple Doppler index (TEI index) that combines systolic and diastolic function can detect LV dysfunction in patients with high levels of plasma BNP in various heart diseases.     

Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure.

OBJECTIVES: The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis. BACKGROUND: Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling. METHODS: We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc., Cleveland, Ohio) in 140 patients with chronic systolic HF (LV ejection fraction <35%) and examined the plasma MPO levels' relationships with echocardiographic indexes of systolic and diastolic performance, as well as long-term clinical outcomes (death, cardiac transplantation, or HF hospitalization). RESULTS: Within the overall cohort, increasing plasma MPO levels were associated with increasing likelihood of more advanced HF (restrictive diastolic stage, right ventricular systolic dysfunction > or =3+, and tricuspid regurgitation area > or =1.8 cm2). Plasma MPO levels were predictive of long-term clinical outcomes (risk ratio [95% confidence interval] = 3.35 [1.52 to 8.86]), even after adjustment for age, LV ejection fraction, plasma B-type natriuretic peptide (BNP), creatinine clearance, or diastolic stage. In receiver-operator characteristic curve analyses, addition of MPO to BNP testing augmented the predictive accuracy of future adverse clinical events (area under the curve 0.66 for BNP only [chi-square test = 12.9, p = 0.0003], and 0.70 for BNP plus MPO [chi-square test = 15.87, p = 0.0004]). CONCLUSIONS: In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes.     

急性冠状动脉综合征患者血清脑钠肽浓度的变化及临床意义

目的:探讨急性冠状动脉综合征(ACS)患者血清脑钠肽(BNP)水平与其冠状动脉病变严重程度及心脏功能的关系。方法:ACS患者81例,分为不稳定型心绞痛(UAP组)组39例和急性心肌梗死组(AMI)组42例,于入院后即刻检测血清BNP水平,并检查冠状动脉病变情况和左室射血分数,分析BNP的水平与冠状动脉病变、心脏功能之间的关系。结果:血清BNP水平随着病情的加重而逐渐升高,AMI组明显高于UAP组,并且从单支病变、双支病变到3支病变BNP水平逐渐增高,两者呈正相关(rs=0.813,P<0.01);随着左室射血分数的降低,BNP水平逐渐升高,两者呈负相关(rs=-0.846,P<0.01)。结论:血清BNP水平与冠状动脉病变程度及心功能相关,可用于ACS患者的危险评估。     

Prognostic impact of plasma brain natriuretic peptide for cardiac events in elderly patients with congestive heart failure

BACKGROUND: Plasma brain natriuretic peptide (BNP) has been reported to be useful in determining the prognosis of patients with ischemic heart disease and cardiomyopathy. However, aging increases the level of plasma BNP; therefore, the prognostic impact of plasma BNP in elderly patients with congestive heart failure has not been fully established. OBJECTIVE: We sought to determine whether plasma BNP could predict recurrent cardiac events in elderly patients with congestive heart failure. METHODS: Forty-eight consecutive elderly patients (>65 years old) were enrolled in the present study. All patients were admitted with their first episode of congestive heart failure. Clinical characteristics, plasma BNP, left ventricular ejection fraction, and left ventricular mass index were compared between patients with and those without recurrent cardiac events. RESULTS: During the follow-up period, twelve cardiac events were observed. The New York Heart Association functional class was signi- ficantly higher in patients with cardiac events than in those without (p < 0.05). The plasma BNP level in pa- tients with cardiac events was significantly higher than in those without (521.0 +/- 156.0 vs. 126.8 +/- 20.1 pg/ml, p<0.001), despite more frequent treatment with angiotensin-converting enzyme inhibitors (75 vs. 28%, p<0.05). The left ventricular ejection fraction was significantly lower and the left ventricular mass index higher in patients with cardiac events as compared with those without (38.1 +/- 5.0 vs. 49.2 +/- 2.4%, p < 0.05; 193.8 +/- 14.3 vs. 132.6 +/- 7.8 g/m(2), p < 0.001, respectively). The plasma BNP was selected as an independent factor associated with cardiac events besides New York Heart Association functional class, left ventricular ejection fraction, and left ventricular mass index using multivariate Cox proportional-hazards regression analysis (hazard ratio = 2.656, p<0.05). The cardiac event rate was significantly higher in patients with a plasma BNP concentration >132 pg/ml using Kaplan-Meier analysis (p < 0.001). Moreover, the plasma BNP level correlated inversely with the length of time from hospital discharge to a cardiac event (r = -0.575, p<0.05). CONCLUSION: Measuring the plasma BNP level before hospital discharge in elderly patients with congestive heart failure was more useful than other conventional examinations for predicting the recurrence of cardiac events.     

Clinical significance of brain natriuretic peptide in patients with postmyocardial infarction

BACKGROUND: Risk stratification after acute myocardial infarction (AMI) includes the evaluation of left ventricular (LV) function. Natriuretic peptides, and particularly brain natriuretic peptide (BNP), emerged as a potential marker of ventricular function and prognosis after AMI. HYPOTHESIS: Brain natriuretic peptide levels are related to ventricular function, either systolic or isolated diastolic, and can give prognostic information in patients surviving AMI. METHODS: In all, 101 patients were enrolled. An echocardiographic (M-mode, two-dimensional, and pulsed Doppler) evaluation was performed and blood samples for BNP measurement were obtained. Clinical events were recorded during 12 months of follow-up. RESULTS: A negative correlation between BNP and LV ejection fraction was observed (r = -0.38; p < 0.001). The BNP levels were higher among patients with LV systolic dysfunction than in patients with isolated diastolic dysfunction (339.1 +/- 249.9 vs. 168.0 +/- 110.5 pg/ml, p = 0.001). The latter had higher levels of BNP than those with normal LV function (68.3 +/- 72.6 pg/ml, p < 0.001). The BNP accuracy to detect LV systolic dysfunction was good (area under the ROC curve [AUC] = 0.83) and increased when isolated diastolic dysfunction was also considered (AUC = 0.87). Brain natriuretic peptide had a very good accuracy in the prediction of death (AUC = 0.95) and the development of heart failure (AUC = 0.90). CONCLUSION: These results extend previous evidence relating BNP to systolic function after AMI. Furthermore, a relationship between BNP levels and diastolic function was found. Brain natriuretic peptide had a very good performance in detecting the occurrence of an adverse event. We conclude that BNP can detect high-risk patients and help select patients for more aggressive approaches.     

Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve stenosis

BACKGROUND: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS. AIM: To assess the release of Nt-BNP in AS with focus on the identification of its main determinants. METHODS: We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay. RESULTS: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050). CONCLUSION: LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.